Toll-like receptor polymorphisms and cerebral malaria: TLR2 Δ22 polymorphism is associated with protection from cerebral malaria in a case control study

Malaria Journal

Research

Peter A Zimmerman¹  Jennifer A Greene¹  James W Kazura¹  Robert O Opoka²  Nadia Sam-Agudu³  Chandy C John³ 

[1] Case Western Reserve University, Wolstein Research Building, 2103 Cornell Rd, 44106, Cleveland, OH, USA;Makerere University, Kampala, Uganda;University of Minnesota, Minneapolis, MN, USA;

关键词: Malaria;    Toll-like receptor;    Plasmodium falciparum;    Polymorphism;    GPI;   

DOI  :  10.1186/1475-2875-11-47

 received in 2011-10-07, accepted in 2012-02-15,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundIn malaria endemic areas, host genetics influence whether a Plasmodium falciparum-infected child develops uncomplicated or severe malaria. TLR2 has been identified as a receptor for P. falciparum-derived glycosylphosphatidylinositol (GPI), and polymorphisms within the TLR2 gene may affect disease pathogenesis. There are two common polymorphisms in the 5' un-translated region (UTR) of TLR2, a 22 base pair deletion in the first unstranslated exon (Δ22), and a GT dinucleotide repeat in the second intron (GTn).MethodsThese polymorphisms were examined in a Ugandan case control study on children with either cerebral malaria or uncomplicated malaria. Serum cytokine levels were analysed by ELISA, according to genotype and disease status. In vitro TLR2 expression was measured according to genotype.ResultsBoth Δ22 and GTn polymorphisms were highly frequent, but only Δ22 heterozygosity was associated with protection from cerebral malaria (OR 0.34, 95% confidence intervals 0.16, 0.73). In vitro, heterozygosity for Δ22 was associated with reduced pam3cys inducible TLR2 expression in human monocyte derived macrophages. In uncomplicated malaria patients, Δ22 homozygosity was associated with elevated serum IL-6 (p = 0.04), and long GT repeat alleles were associated with elevated TNF (p = 0.007).ConclusionReduced inducible TLR2 expression may lead to attenuated pro-inflammatory responses, a potential mechanism of protection from cerebral malaria present in individuals heterozygous for the TLR2 Δ22 polymorphism.

【 授权许可】

Unknown   
© Greene et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.